This is a proposal to continue follow-up of the Wisconsin Diabetes Registry, a unique population-based cohort of 595 individuals enrolled at diagnosis of insulin-dependent diabetes mellitus (IDDM) and closely monitored for up to 5 years. Glycemic control and microvascular status have been described comprehensively from the time of diagnosis for all subjects newly diagnosed with IDDM living in a geographically defined area of central and southern Wisconsin and less than 30 years of age at diagnosis. Such information puts this study in a critical position to make a substantial contribution to the understanding of progression and correlates of long term complications of diabetes. The primary goals in following up this cohort are to: 1) determine incidence and progression of nephropathy, retinopathy and neuropathy 6 to 10 years after diagnosis of diabetes; 2) quantify the relationship between incidence and progression of these complications and longitudinal glycemic control, other medical conditions (e.g., hypertension), familial factors (e.g., parent or sibling hypertension), puberty stage and gender, age at diagnosis of diabetes, selected physiologic and genetic characteristics (e.g., genetic markers, IGF-I); 3) determine how age, gender, endogenous insulin, medical management, self-management and economic status influence glycemic control after 6-10 of diabetes; 4) determine the incidence of acute diabetes-related complications after 6-10 years of diabetes and determine the relationship of this incidence to recent and longitudinal glycemic control. New emphasis in this proposal is placed on factors that may correlate with microvascular complications independent of glycemic control. Microvascular complications are present in the majority of individuals with diabetes within 10 years of diagnosis. This study provides the only large population based cohort that can be evaluated during the interval when microvascular complications are most likely to develop. This study will provide a precise description of the time course in which complications evolve, singly or in synergistic combinations. Only by understanding the evolution of complications and factors that influence their chronology will it be possible to identify characteristics that may identify persons at high risk. Intensive preventive and therapeutic interventions could then be focused on such high risk persons.